1. Field of the Invention
This invention relates to implantable medical devices, such as stents, and a method of resolving ischemia by inducing formation of new blood vessels through angiogenesis and arteriogenesis.
2. Description of the Background
A major component of morbidity and mortality attributable to cardiovascular disease occurs as a consequence of the partial or complete blockage of vessels carrying blood in the coronary and/or peripheral vasculature. When such vessels are occluded, various complications may result from death of tissue previously nourished by the occluded vessels or inability of the occluded vessels to transport sufficient blood supply to regions requiring high blood consumption and accompanying nutrients.
Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels. Such mechanical enhancements are often provided by employing surgical techniques that attach natural or synthetic conduits proximal and distal to the areas of occlusion, thereby providing bypass grafts, or revascularization by various means to physically enlarge the vascular lumen at the site of occlusion. These revascularization procedures involve such devices as balloons, endovascular knives (atherectomy), and endovascular drills. The surgical approach is accompanied by significant morbidity and even mortality, while the angioplasty-type processes are complicated by recurrent stenoses in many cases.
In some individuals, blood vessel occlusion is partially compensated by the natural process of therapeutic angiogenesis, in which new vessels are formed to replace the function of the impaired vessels. These new conduits may facilitate restoration of blood flow to the deprived tissue, thereby constituting xe2x80x9cnatural bypassesxe2x80x9d around the occluded vessels. However, some individuals are unable to generate sufficient new vessels to adequately compensate for the diminished blood flow caused by cardiovascular disease. Accordingly, it would be desirable to provide methods and systems for delivering agents to help stimulate the natural process of therapeutic angiogenesis in occluded coronary and peripheral arteries in order to treat ischemia.
A stent is provided. The stent includes a tubular body having an outer surface for contacting the wall of a vessel and an inner surface. The stent also includes a first coating supported by the inner surface and containing an angiogenic substance for the release of the angiogenic substance in the vessel. In addition, the stent includes a second coating supported by the outer surface and containing a therapeutic substance for applying the therapeutic substance to the wall of the vessel.
In some embodiments, the therapeutic substance is selected from antiproliferative, antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antioxidant, and anti-migratory substances, inhibitors of matrix synthesis, and combinations thereof.
Also provided is a stent, which includes a tubular structure having an inner surface and an outer surface, for implanting in a blood vessel. The stent includes a first therapeutic substance carried by the inner surface for being released downstream with the flow of blood and a second therapeutic substance, which is different from the first therapeutic substance, carried by the outer surface for application to the blood vessel wall. The first therapeutic substance facilitates therapeutic angiogenesis, and the second therapeutic substance inhibits migration or proliferation of smooth muscle cells.
In one embodiment, the inner surface of the stent includes a plurality of cavities for releasing the first therapeutic substance when exposed to the flow of blood. In another embodiment, the inner surface includes a plurality of cavities for releasing the first therapeutic substance when exposed to the flow of blood, and the outer surface includes a plurality of cavities for applying the second therapeutic substance to the blood vessel wall.
A method for increasing blood flow to ischemic tissues located downstream from an occluded region in a blood vessel is also provided. The method includes implanting a stent in the blood vessel at a location upstream from the ischemic tissues. The stent has an inner surface carrying an angiogenic substance.
In one embodiment, the stent is positioned at a location upstream of the occluded region. In another embodiment, the stent is positioned across at least a portion of the occluded region.
In yet another embodiment, the stent additionally includes a coating disposed on the outer surface of the stent. The coating includes a therapeutic substance. In another embodiment, the stent includes cavities on the outer surface containing a therapeutic substance.